The role of Tsukushi (TSK), a small leucine-rich repeat proteoglycan, in bone growth

INTRODUCTION: Endochondral ossification is one of a key process for bone maturation. Tsukushi (TSK) is a novel member of the secreted small leucine-rich repeat proteoglycan (SLRP) family. SLRPs localize to skeletal regions and play significant roles during whole phases of bone development. Although prior evidence suggests that TSK may be involved in the regulation of bone formation, its role in skeletal development has not yet been elucidated. METHODS: In the present study, we examined TSK's function during bone growth by comparing skeletal growth of TSK deficient (TSK−/−) mice and wild type (WT) mice. And an in vitro experiment using siRNA transfection of a chondrogenic cell line was performed. RESULTS: TSK−/− mice exhibited decreased weight and short stature at 3 weeks of age due to decreased longitudinal bone growth coupled with low bone mass. Furthermore, an in vitro experiment using siRNA transfection into a chondrogenic cell line revealed that decreased TSK expression induced down-regulation of key chondrogenic marker gene expression and up-regulation of mid-to-late chondrogenic markers gene expression. CONCLUSIONS: Our results reveal that TSK regulates bone elongation and bone mass by modulating growth plate chondrocyte function and consequently, overall body size.